Development of autoimmunity in Lyme arthritis

Treatment-resistant Lyme arthritis (TRLA) develops in 10% of Lyme arthritis patients and is characterized by continuous joint inflammation that does not resolve with antibiotic therapy. TRLA is associated with HLA-DRB1*0401 and related alleles, as well as with an immune response to the Borrelia burgdorferi (Bb) outer surface protein A (OspA). The immunodominant epitope of OspA in the context of HLA-DRB1*0401 corresponds to amino acids 165-173 (OspA165-173). The human Lymphocyte Function Antigen-1 (hLFA1alpha) contains a peptide with homology to OspA165-173. Treatment-resistant Lyme arthritis patients' T cells, cloned based on their ability to bind OspA165-173-loaded HLA-DRB1*0401 tetramers, respond to OspA and hLFA1alpha with a different cytokine profile, suggesting that hLFA1alpha acts as a partial agonist with a potential role in the perpetuation of joint inflammation.